Replacement heart valves and their methods of use and manufacture

ABSTRACT

A prosthetic valve has a support structure that meets with a plurality of leaflets capable of transitioning between open and closed states. The support structure can include a base frame with a polymer coating and the leaflets can be artificial. The interface between the support structure and each leaflet can be at least partially convex when viewed from an exterior of the support structure along a normal to a plane formed by a central axis of the support structure and a central axis of the leaflet.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional application of U.S. patent applicationSer. No. 14/611,071, filed Jan. 30, 2015, which claims the benefit ofand priority to U.S. Provisional Patent Application Ser. No. 61/991,354,filed May 9, 2014, both of which are incorporated by reference herein intheir entirety and for all purposes.

FIELD

The subject matter described herein relates generally to improvedreplacement valves, such as for the aortic and mitral valves of theheart.

BACKGROUND

The human heart has a number of valves for maintaining the flow of bloodthrough the body in the proper direction. The major valves of the heartare the atrioventricular (AV) valves, including the bicuspid (mitral)and the tricuspid valves, and the semilunar valves, including the aorticand the pulmonary valves. When healthy, each of these valves operates ina similar manner. The valve translates between an open state (thatpermits the flow of blood) and a closed state (that prevents the flow ofblood) in response to pressure differentials that arise on oppositesides of the valve.

A patient's health can be placed at serious risk if any of these valvesbegin to malfunction. Although the malfunction can be due to a varietyof reasons, it typically results in either a blood flow restrictingstenosis or a regurgitation, where blood is permitted to flow in thewrong direction. If the deficiency is severe, then the heart valve mayrequire replacement.

Substantial effort has been invested in the development of replacementheart valves, most notably replacement aortic and mitral valves.Replacement valves can be implanted percutaneously by way of atransfemorally or transapically introduced catheter, or can be implanteddirectly through open heart surgery. The replacement valves typicallyinclude an arrangement of valve leaflets that are fabricated fromporcine tissue or an artificial material such as a polymer. Theseleaflets are maintained in position by a stent or support structure.

FIG. 1A is a perspective view depicting a prior art prosthetic heartvalve 8 of U.S. Pat. No. 7,682,389 (“Beith”). This valve 8 can beimplanted directly and includes a stent 10 and three leaflets 30. Whenimplanted, blood is permitted to flow from the upstream (blood inlet)end 14 towards the downstream (blood outlet) end 12, but is preventedfrom flowing in the reverse direction by the presence of leaflets 30.Leaflets 30 have free edges 34 located on the downstream end 12. Eachleaflet 30 also has a fixed edge (or interface) 32 joined with scallopededge portions 16 a, 16 b, and 16 c, respectively, of stent 10. Across-sectional plane “I” is shown that bisects the leaflet 30 joinedwith fixed edge 16 a (located at front right). Cross-sectional plane “I”is parallel to the direction of the flow of blood and thus is verticalin FIG. 1A.

FIG. 1B is a side view of a right-side portion of valve 8 after rotationsuch that plane “I” is aligned with the page. From the reader'sperspective FIG. 1B is viewed along a normal to plane “I” From thisview, the entirety of fixed edge 32 of leaflet 30 (which is aligned withedge 16 a) lies in a flat plane and is straight with no curvature.

FIG. 1C is a side view of a right-side portion of another prior artvalve 8 after rotation such that plane “I” is aligned with the page(like the case with FIG. 1B). Here, fixed edge 32 is fully concave fromthe perspective exterior to valve 8. In the prior art, this fullyconcave shape was believed to assist in the movement of the leaflet fromthe open position to the closed position where the leaflet is pushed ordraped into the valve interior, as adequate coaptation in the closedstate is essential for the proper functioning of the valve.

However, the flat and fully concave shapes of the prior art designsdescribed with respect to FIGS. 1A-1C can lead to a valve withcompromised hydrodynamic efficiency due to the fact that the localleaflet length at various heights of the valve is not long enough. Thiscan lead to inadequate valve opening. It can also (or alternatively)lead to local bulging and tightness. The flat or fully concave shapescan both result in localized stress concentrations that, in combinationwith the aforementioned bulging and tightness, can result in reduceddurability and premature failure.

U.S. Pat. No. 6,613,086 (“Moe”) describes other variations in the shapeof the support structure (or valve body) for a directly implantablevalve. Moe describes “an attachment curve” that is defined as theposition where the leaflets are coupled along the inner wall of thesupport structure. Moe seeks to increase the durability of each leafletcoupled to the support structure by moving the leaflet's point ofmaximum loaded stress along the attachment curve and away from thelocation of any stress risers. Moe does this by adjusting the radius ofthe support structure at different heights along the support structure'saxis of flow (see numeral 26 of FIG. 1) and at different radialpositions within each cross-sectional plane taken perpendicular to andat different heights along the support structure's axis of flow. As aresult, Moe's support structures have substantially non-circular ornon-cylindrical inner walls along the attachment curve. These supportstructures can have significantly asymmetric shapes with substantialsurface variations, as evidenced by the bulges 58 and 60 described withrespect to FIG. 11 of Moe. Moe's support structures are neithercylindrical nor substantially cylindrical as those terms are usedherein.

While trying to reduce the localized stress, Moe's approaches lead tolocal lengthening of the leaflet at that height in the valve. This locallengthening will lead to an increase in the resistance of the leaflet toopen and could compromise the full opening of the valve, leading tolocal bulging in the leaflet surface. This, in turn, will reduce thehydrodynamic efficiency of the valve and potentially reduce thedurability of the valve leaflet.

For these and other reasons, needs exist for improved prosthetic valves.

SUMMARY

Example embodiments of improved prosthetic heart valves and theirmethods of use and manufacture are provided herein. In some of theseexample embodiments, the prosthetic heart valve can include: a supportstructure having a central axis oriented in the direction of blood flowthrough an interior of the support structure; and a plurality ofartificial leaflets, each leaflet having a base along the supportstructure and a free edge allowed to move independent of the supportstructure. Each leaflet can also have a central axis extending betweenthe base and the free edge. The support structure can be substantiallycylindrical where the base of each leaflet meets the support structure.The artificial leaflets can be adapted to move between a first position,for preventing the flow of blood through an interior of the supportstructure, and a second position, for allowing the flow of blood throughthe interior of the support structure. For each leaflet, a profile ofthe base of the leaflet can be at least partially convex when viewedfrom an exterior of the support structure along a normal to a planeformed by the central axis of the support structure and the central axisof the leaflet. Additional embodiments are also disclosed.

Other systems, methods, features and advantages of the subject matterdescribed herein will be or will become apparent to one with skill inthe art upon examination of the following figures and detaileddescription. It is intended that all such additional systems, methods,features and advantages be included within this description, be withinthe scope of the subject matter described herein, and be protected bythe accompanying claims. In no way should the features of the exampleembodiments be construed as limiting the appended claims, absent expressrecitation of those features in the claims.

BRIEF DESCRIPTION OF FIGURES

The patent or application file contains at least one drawing executed incolor. Copies of this patent or patent application publication withcolor drawing(s) will be provided by the Office upon request and paymentof the necessary fee.

The details of the subject matter set forth herein, both as to itsstructure and operation, may be apparent by study of the accompanyingfigures, in which like reference numerals refer to like parts. Thecomponents in the figures are not necessarily to scale, emphasis insteadbeing placed upon illustrating the principles of the subject matter.Moreover, all illustrations are intended to convey concepts, whererelative sizes, shapes and other detailed attributes may be illustratedschematically rather than literally or precisely.

FIG. 1A is a perspective view depicting a prior art prosthetic heartvalve.

FIG. 1B is a side view of a right-hand portion of the prior art valveafter rotation such that plane “I” is aligned with the page.

FIG. 1C is a side view of a right-hand portion of another prior artvalve after rotation such that plane “I” is aligned with the page.

FIGS. 2A-B are perspective views of the front half of an exampleembodiment of a support structure for a prosthetic heart valve.

FIGS. 2C-D are top down views of an example embodiment of prostheticvalve leaflets in open and closed states, respectively.

FIG. 2E is an illustrative view depicting a portion of an exampleembodiment of a prosthetic valve in a laid flat state.

FIGS. 2F-H are perspective views of an example embodiment of aprosthetic heart valve.

FIGS. 2I-J are perspective views of an example embodiment of aprosthetic heart valve in line drawing and surface shaded forms,respectively.

FIG. 2K is a perspective view of an example embodiment of a prostheticheart valve.

FIG. 3A is a color top down view comparing the positions of two sets ofleaflets in their open states, where the support structure is not shown.

FIG. 3B is a color perspective view comparing the positions of two setsof leaflets in their open states within the front half of a prostheticheart valve where the support structure is not shown.

FIG. 3C is a color top down view comparing the positions of two sets ofleaflets in their closed states, where the support structure is notshown.

FIG. 3D is a color perspective view comparing the positions of two setsof leaflets in their closed states within the front half of a prostheticheart valve where the support structure is not shown.

FIG. 3E is a color perspective view depicting an example embodiment ofleaflets in their open state with the stress levels experienced atvarious positions across the surface of the leaflets, where the supportstructure is not shown.

FIG. 3F is a color perspective view depicting conventional leaflets intheir open state with the stress levels experienced at various positionsacross the surface of the leaflets, where the support structure is notshown.

FIG. 3G is a color perspective view depicting an example embodiment ofleaflets in their closed state with the stress levels experienced atvarious positions across the surface of the leaflets, where the supportstructure is not shown.

FIG. 3H is a color perspective view depicting conventional leaflets intheir closed state with the stress levels experienced at variouspositions across the surface of the leaflets, where the supportstructure is not shown.

FIG. 3I is a color top down view depicting an example embodiment ofleaflets in their closed state with the stress levels experienced atvarious positions across the surface of the leaflets, where the supportstructure is not shown.

FIG. 3J is a color top down view depicting conventional leaflets intheir closed state with the stress levels experienced at variouspositions across the surface of the leaflets, where the supportstructure is not shown.

FIG. 3K is a color frontal view depicting an example embodiment of aleaflet mapped with the simulated relative degree of vertical strainenergy release.

FIG. 3L is a color frontal view depicting a conventional leaflet mappedwith the simulated relative degree of vertical strain energy release.

FIG. 3M is a color frontal view depicting an example embodiment of aleaflet mapped with the simulated relative degree of lateral strainenergy release.

FIG. 3N is a color frontal view depicting a conventional leaflet mappedwith the simulated relative degree of lateral strain energy release.

FIGS. 4A-B are perspective views depicting the front half of additionalexample embodiments of a support structure.

FIG. 5A is a flowchart depicting an example embodiment of a method ofmanufacturing a prosthetic heart valve.

FIG. 5B is a photograph depicting an example embodiment of a mandrel foruse in a dip casting manufacturing method.

FIG. 5C is a photograph depicting an example embodiment of a base framefor use in a dip casting manufacturing method.

DETAILED DESCRIPTION

Before the present subject matter is described in detail, it is to beunderstood that this disclosure is not limited to the particularembodiments described, as such may, of course, vary. It is also to beunderstood that the terminology used herein is for the purpose ofdescribing particular embodiments only and is not intended to belimiting.

Example embodiments of systems, devices, kits, and methods are providedherein that relate to valve replacement in a patient. These embodimentswill be described primarily with respect to replacement of the naturalaortic heart valve with a prosthetic heart valve having three artificial(i.e., man-made) leaflets. However, the scope of the present disclosureis not limited to such, and can likewise be applied to prosthetics forreplacement of other valves of the heart (e.g., mitral) where thoseprosthetics have two or more leaflets. These prosthetics may also beused to replace valves in other locations in the patient's body outsideof the heart.

The example embodiments of the prosthetic valves disclosed herein are,in many cases, designed in a manner different from those manners taughtby the prior art. FIGS. 2A-B are perspective front views and FIGS. 2C-Dare top down views of one such example embodiment of a prosthetic valve100. Referring to FIG. 2A, a support structure 102 meets a plurality ofvalve leaflets 110-1, 110-2, and 110-3. Each of leaflets 110 can bediscrete from the others (as shown here) or can be portions of oneunitary (monolithic) leaflet body.

Support structure 102, which can also be referred to as a stent, isconfigured to allow blood to flow in direction 101 and has an upstreamend 103 and a downstream end 104. Support structure 102 also includes anannular base portion 105 that can have a planar or flat upstreamterminus (not shown) or that can have a curved or scalloped upstreamterminus as shown here. Support structure 102 also includes threeextensions 106 that project from annular base portion 105 towardsdownstream end 104.

Extensions 106 include curved interfaces 107, which are located directlyon an edge in this embodiment. Here, each curved interface 107 is thelocation where support structure 102 meets the operable base 111 of aleaflet 110. In many embodiments curved interfaces 107 and the leafletbases 111 will coincide.

In the embodiment depicted in FIG. 2A, support structure 102 is in theform of a base frame. The leaflets can be integrally formed on this baseframe 102, such as through a casting (e.g., dip casting) or moldingprocess. A dip casting process that is suitable for formation of theleaflets is described with respect to FIGS. 5A-C. In an example of a dipcasting process, the base frame 102 is placed on a mandrel and dipped ina polymer, which results in the formation of leaflets integrated with apolymeric coating over the base frame. Here, curved interfaces 107 referto the boundary between support structure 102 and each of the integratedleaflets (i.e., base 111 of each leaflet). Depending on the particularimplementation, curved interfaces 107 can coincide with the downstreamedge of the base frame itself or the downstream edge of the coating overthe base frame.

In some embodiments, leaflets 110 (whether they be tissue or artificial)can be physically joined to support structure 102 through a couplingprocess such as sewing. FIG. 2E is an illustration of an exampleembodiment of a portion of valve 100 in a laid flat state. Here, leaflet110-1 has been coupled to support structure 102 by a seam 201 created bysewing a suture 202 through leaflet 110-1 and support structure 102. Thephysical base edge 204 of leaflet 110 can be located upstream from seam201 (as shown), folded back into a location downstream of seam 201, orotherwise. In these embodiments, both curved interface 107-1 and base111-1 refer to the transition between the secured portion of leaflet110-1 and the operable portion of leaflet 110-1 that is free totransition or deflect between the open and closed states, which in theembodiment of FIG. 2E coincides with the upstream edge of supportstructure 102.

Referring back to FIG. 2A, annular base portion 105 also includesflanges 108 and 109 between which a sewing cuff (not shown) can beplaced. As an alternative for all of the embodiments described herein,only a single flange 108 may be present, or the flanges 108 and 109 canbe omitted altogether. In light of this description, those of ordinaryskill in the art will readily understand the design and appearance of asewing cuff and how it can be coupled with one or more flanges ofsupport structure 102.

In FIG. 2A, support structure 102 is positioned according to theperspective depicted by line 2A-2A of FIG. 2C. Stated differently,cross-sectional plane “I” of FIG. 2C is parallel to the page of FIG. 2Asuch that the viewer views FIG. 2A along a normal “N” to plane “I”.Plane “I” can also be described as extending through a central axis ofvalve 100 oriented in the direction of blood flow (indicated by thesolid circle at the tip of the normal “N” arrow in FIG. 2C) and acentral axis of the respective leaflet extending between base 111 andfree edge 112. An example of the central axis 114-1 is where plane “I”intersects leaflet 110-1 in FIGS. 2C-D. There, plane I is a center planeor mid-plane to leaflet 110-1.

FIG. 2B depicts the embodiment of FIG. 2A in an annotated form to allowcomparison with the flat downstream edges 70-1 and 70-2 that would bepresent if support structure 102 was shaped according to the prior artapproach of FIGS. 1A-B. Here, interfaces 107-1 and 107-2 can be seen tobulge in a pronounced fashion from flat edges 70-1 and 70-2. Note thatedge 70-2 is referred to as flat because it would appear flat if supportstructure 102 were rotated to place edge 70-2 in the position of edge70-1 in FIG. 2B. The bulges of interface 107-1 and 107-2 would be evenmore pronounced if compared to the prior art concave edge approach ofFIG. 1C. Although interface 107-3 and 70-3 are not shown, the samerelationships would present for those as well.

FIG. 2C depicts leaflets 103 in their open positions with supportstructure 102 omitted. However, were support structure 102 to be shown,apex A1 of extension 106-1 and apex A2 of extension 106-2 (both shown inFIG. 2A) would be positioned as noted in FIG. 2C.

Leaflets 103 each have a free edge 112 that moves independent of supportstructure 102. FIG. 2D depicts leaflets 110 after movement to theirclosed positions. In the closed position, in many embodiments themajority of free edges 112 will be in contact with each other. In someembodiments, the entirety of free edges 112 will be in contact with eachother.

As seen in FIG. 2A, interface 107-1 is partially convex and concave fromthe perspective exterior to valve 100. Interface 107-1 coincides withbase 111-1 of leaflet 130-1 (see FIGS. 2I-K). The convex portion 120 ismidway along interface 107-1. Convex portion 120 is convex in twodimensions, e.g., like a portion of the border of a two-dimensionalellipse from the perspective of outside the ellipse.

Concave portions 121-1 and 121-2 can be present on both sides of theconvex middle portion 120. As seen in FIG. 2A, concave portion 121-1 hasa significantly lower degree of curvature than convex middle portion120. The combination of a convex portion with one or more concaveportions gives interface 107-1 an undulating appearance when viewed fromthis perspective. This appearance can also be referred to as S-shaped ormulti-curved if there is at least one concave portion and at least oneconvex portion (e.g., two concave portions and two convex portionsqualifies as S-shaped), and those portions can vary in height and degreeof curvature. In some embodiments, interface 107-1 can be convex alongits entire height (or length). In other embodiments, interface 107-1 caninclude a convex portion with a flat (or linear) portion on one or bothsides. In still other embodiments, interface 107-1 can include a convexportion in combination with any number of flat portions and concaveportions.

FIG. 2F is a perspective front view of another example embodiment of asupport structure 102 for a prosthetic valve 100. In this embodiment,the degree of curvature present in convex portion 120 and concaveportions 121-1 and 121-2 is relatively less than in the embodimentdescribed with respect to FIG. 2A. FIG. 2G is a perspective front viewof the embodiment of FIG. 2F annotated to allow comparison of interfaces107-1 and 107-2 with prior art edges 70-1 and 70-2 (described withrespect to FIG. 2B).

In FIGS. 2F-G, only the front half of support structure 102 is shown(i.e., forward of plane “I”), with the back half and valve leaflets 110omitted for ease of illustration. The entire support structure 102 isdepicted in the perspective view of FIG. 2H. FIGS. 2I-2J are a linedrawing perspective view and surface shaded perspective view,respectively, of the embodiment of FIG. 2F with leaflets 110 included.FIG. 2K is a line drawing perspective view of the embodiment of FIG. 2Ftaken from a different perspective than that of FIG. 2I.

In addition to being described as “convex,” certain convex portions ofinterface 107-1 can be described as tapering at an increasing rate asthe distance increases from upstream end 103. Characterized in yetanother manner, the convex curve may be regarded as “concave down” withrespect to a straight line reference similar to edge 70-1 described withrespect to FIG. 2B. The convexity may change in direction to “concaveup” (i.e., change in mathematical sign considering a second derivativeof interface 107-1) and/or may change in magnitude (i.e., in terms ofdegree of curvature) along the length of interface 107-1.

For all of the embodiments described herein, any of the aforementionedshapes can likewise be present on interfaces 107-2 and 107-3 when thoseinterfaces 107-2 and 107-3 are viewed from the same perspective asinterface 107-1 in FIG. 2A. Preferably, each of interfaces 107-1, 107-2and 107-3 has the same shape to maximize the synchronous motion ofleaflets 110, as significantly asynchronous motion can negatively impactthe durability of valve 100. However, each interface 107 can vary inshape with respect to the others provided that the durability of valve100 remains acceptable.

While support structure 102 can take various shapes, in all embodiments,support structure 102 can be substantially cylindrical or cylindrical.As those of ordinary skill in the art understand, being “cylindrical”does not require support structure 102 to be in the form of a fullgeometric cylinder (e.g., vertical walls oriented at a right angle to acircular cross-section), but rather requires support structure 102 tolie along a part of a hypothetical geometric cylinder (with only minordeviation). For example, the entire inner lumen surface (the surfacedirectly adjacent the flow of blood) of support structure 102 asdepicted in FIG. 2D is cylindrical as that term is used herein.Similarly, those of ordinary skill in the art understand that a supportstructure 102 that is “substantially cylindrical” is permitted greaterdeviation from a mathematical cylinder than simply “a cylindricalsupport structure” and would readily recognize those support structuresthat qualify as being substantially cylindrical.

While the entirety of support structure 102 can be cylindrical orsubstantially cylindrical, it is also the case that only part of supportstructure 102 can be cylindrical or substantially cylindrical, with theremaining part of support structure 102 being non-cylindrical. Forinstance, in the embodiment described with respect to FIG. 2D, althoughthe entire inner lumen surface of support structure 102 is cylindrical,the opposite outer surface has flanges 108 and 109 that are notcylindrical.

In other embodiments, only the portion of support structure 102 alongcurved interfaces 107 (e.g., along base 111 of leaflets 110) may becylindrical or substantially cylindrical. Such a configurationdistinguishes over the subject matter of U.S. Pat. No. 6,613,086 (“Moe”)described herein.

When support structure 102 is formed from a base frame coated inpolymer, then in some embodiments, only the base frame (either theentirety or a portion thereof) can be cylindrical or substantiallycylindrical, while the outer surface of the polymer coating is notcylindrical or not substantially cylindrical. For example, in someembodiments the inner lumen surface of a base frame is cylindrical andthe outer surface of the polymer coating (along the inner lumen of thebase frame) is substantially cylindrical (or even non-cylindrical) dueto variations in the coating thickness.

In the embodiments of FIGS. 2A-B and 2F-K, valve 100 is sized to fit a23 millimeter (mm) aortic tissue annulus, although this embodiment canbe sized at other standard dimensions as well, such as 17 mm, 18 mm, 19mm, 20 mm, 21 mm, 22 mm, 24 mm, 25 mm, 26 mm, 27 mm, 28 mm, and 29 mm,as well as dimensions that lie in between. These dimensions are commonlyreferred to as the inner diameter or “ID” of valve 100, which is thelateral dimension of the valve at a position commensurate with leaflets110. The valve may have an even larger lateral dimension elsewhere, suchas the location of the sewing cuff.

FIG. 4A depicts another embodiment of valve 100 (in a view similar tothat of FIG. 2A). In this embodiment, valve 100 is sized for a 19 mmtissue annulus. Interface 107-1 includes a convex portion 401 with asmaller flat or concave portion 402 near apex A1 of extension 106-1.Interface 107-1 of valve 100 can again be seen to bulge in a pronouncedconvex fashion from the overlaid flat edge 70-1. Interface 107-2 and107-3 (not shown) have similar shapes.

FIG. 4B depicts another embodiment of valve 100 (again in a view similarto that of FIG. 2A). In this embodiment, valve 100 is sized for a 27 mmtissue annulus. Interface 107-1 is S-shaped with a first slightly convexportion 403 adjacent apex A1, a concave portion 404 immediately upstream(below), and a second slightly convex portion 405 upstream from (below)concave portion 404. Overlaid flat edge 70-1 is again present to furtherillustrate the differences with interface 107-1 of this embodiment ofvalve 100. Interface 107-2 and 107-3 (not shown) have similar shapes.

The embodiments of valve 100 described herein are suitable forimplantation in the body of a patient using any number of medicalprocedures. Preferably, these embodiments of valve 100 are for directimplantation to the aortic annulus using open heart surgery. Suchembodiments of valve 100 are not radially collapsible for insertion intoan intravascular delivery device (e.g., a catheter) or a transapicaldelivery device. However, in other embodiments, valve 100 can beconfigured with a radially collapsible support structure 102 that allowsthe lateral dimension of valve 100 to be reduced by a degree sufficientto permit the insertion into an appropriately sized intravascular ortransapical delivery device.

All of the embodiments of valve 100 described herein can also beprovided to a medical professional (or retained by a medicalprofessional) as part of a kit (or a set) of prosthetic valves beingsized for various tissue annulus dimensions. The sizes can include anycombination of two or more of the following: 17 mm, 18 mm, 19 mm, 20 mm,21 mm, 22 mm, 23 mm, 24 mm, 25 mm, 26 mm, 27 mm, 28 mm, and 29 mm. Inone embodiment, the kit includes at least one valve 100 configured withan at least partially convex interface 107 as described herein, alongwith one or more valves having different configurations. In anotherembodiment, for each labeled size, the kit includes at least one of theembodiments of a valve 100 described herein. In still anotherembodiment, the kit includes a 19 mm valve 100 in the form of theembodiment described with respect to FIG. 4A, a 23 mm valve 100 in theform of the embodiment described with respect to FIG. 2F, and a 27 mmvalve 100 in the form of the embodiment described with respect to FIG.4B.

Support structure 102 can be fabricated from any desired material, suchas polymers (e.g., polyether ether ketones (PEEK), polyurethanes, etc.),metals (e.g., nitinol, stainless steel, etc.), and others. Leaflets 110are fabricated from an artificial polymeric material, including anybiostable polyurethanes and polyurethane compositions (e.g.,polysiloxane-containing polyurethanes, etc.) known in the art. Examplesof polyurethane containing leaflets are described in U.S. Pat. No.6,984,700, U.S. Pat. No. 7,262,260, U.S. Pat. No. 7,365,134, and Yilgoret al., “Silicone containing copolymers: Synthesis, properties andapplications,” Prog. Polym. Sci. (2013), all of which are incorporatedby reference herein in their entirety for all purposes. Materials thatapproach ideal isotropic non-creeping characteristics are particularlysuitable for use in many embodiments. While many materials can be used,it is preferable that the selected material have the appropriate modulusof elasticity to allow leaflets 110 to readily and repeatedly transitionbetween the open and closed states without succumbing to fatigue orstress related failure. In many example embodiments, the modulus ofelasticity for leaflets 110 is in the range of 10-45 MegaPascals (MPa).In certain other example embodiments, the modulus of elasticity forleaflets 110 is in the range of 20-30 MPa.

Valves 100 designed in accordance with the embodiments described hereinexhibited superior performance over previous valves in a number ofrespects. For example, FIGS. 3A-N are a series of simulation outputsthat compare the performance of leaflets of an embodiment of a 23 mmvalve 100 having leaflets 110 (similar to that described with respect toFIGS. 2F-K) as compared to a valve having a flat edge 70 with leaflets72 similar to the prior art approach described with respect to FIGS.1A-B as well as FIGS. 2B, 2G, and 4A-B. Such comparisons demonstrate theimproved performance of the at least partially convex edge embodimentsover the prior art flat edge approach (as well as the prior art concaveedge approach described with respect to FIG. 1C).

FIG. 3A is a top down view of leaflets 110 (blue) in their open positionas compared to leaflets 72 (red) each having a base that would beattached to flat edge 70. It is seen here that the free edges ofleaflets 110 approach the wall of support structure 102 (not shown) muchmore closely than the free edges of leaflets 72 and thus providesignificantly less resistance to blood flow through the interior ofvalve 100. This is shown further in FIG. 3B, which is a view of openleaflets 110 in an orientation corresponding to that of FIG. 2F butwithout showing support structure 102. The visible surfaces are thosethat are closest to the viewer. Almost the entirety of leaflets 110 arecloser to the viewer than leaflets 72, resulting in a larger interiorspace through which blood can flow.

FIG. 3C is a top down view of leaflets 110 (blue) in their closedposition as compared to leaflets 72 (red). Visible surfaces indicatethose that are closest to the viewer looking into valve 100 from thedownstream end. Leaflets 110 extend further into the interior of valve100 than leaflets 72, and achieve a higher degree of coaptation and thusa better seal against backflow and regurgitation, particularly in thecenter where all three of leaflets 110 meet. Leaflets 110 also eliminatethe buckled or dimpled portion that is present in each of leaflets 72and seen as the circular spots. Leaflets 110 of FIG. 3C is shown from adifferent perspective in FIG. 3D.

FIG. 3E is a perspective of leaflets 110 in the open position showingthe stress levels experienced at various positions across the surface ofleaflets 110. In FIGS. 3E-N, increasing relative stress is indicated bycolor in the following order: dark blue (lowest relative stress), lightblue, green, yellow, orange, and red (highest relative stress). Themaximum principal stress experienced by leaflets 110 was calculated tobe 2.64 (MPa). This is compared to leaflets 72 of FIG. 3F, which isshown on the same scale as FIG. 3E and indicates that leaflets 72generally experience higher stress, particularly across the centerregion of leaflets 72 and along the mid-region of the bases. The maximumprincipal stress experienced by leaflets 72 was calculated to be 2.75MPa.

FIG. 3G is a perspective of leaflets 110 in the closed position showingthe stress levels experienced at various positions across the surface ofleaflets 110. The maximum principal stress experienced by leaflets 110in this position was calculated to be 2.75 MPa. FIG. 3H, which is shownon the same scale as FIG. 3G, indicates that leaflets 72 experiencehigher stress in pockets positioned on both sides of each leaflet 72near the junction of the free edge and base. The maximum principalstress for leaflet 72 was 3.005 MPa, which is again higher than forleaflets 110.

FIG. 3I is a top down view of the simulation of leaflets 110 in FIG. 3Gand FIG. 3J is a top down view of the simulation of leaflets 72 in FIG.3H. This comparison shows the higher degree of coaptation achieved byleaflets 110, particularly at the center of valve 100 and where adjacentfree edges meet in proximity to the support structure (not shown).

FIG. 3K is a front view of leaflet 110 mapped with the simulatedrelative degree of vertical strain energy release. FIG. 3L is a frontview of leaflet 72 showing the simulated relative degree of verticalstrain energy release according to the same scale as FIG. 3K. FIG. 3M isa front view of leaflet 110 mapped with the simulated relative degree oflateral strain energy release. FIG. 3N is a front view of leaflet 72showing the simulated relative degree of lateral strain energy releaseaccording to the same scale as FIG. 3M.

Strain energy release is determined by an integral across the entirecycle of motion of the leaflet, i.e., movement between the open andclosed positions and back. Vertical strain energy release is ameasurement of how much energy is present at each position on theleaflet to drive the growth of a defect in the vertical direction, i.e.,between bottom and top as shown in FIGS. 3K-L. Lateral strain energyrelease is a measurement of how much energy is present at each positionon the leaflet to drive the growth of a defect in the lateral direction,i.e., between left and right sides as shown in FIGS. 3M-N.

As can be seen in FIGS. 3K-L, leaflet 110 experiences significantlyreduced vertical strain energy release, which was calculated to be110.331 joules per mm squared (J/mm2), as compared to 132.151 J/mm2 forleaflet 72. The most significantly reduced regions are shown in thelower center portion of leaflet 110 and in the upper corners of leaflet110 where the free edge and base come together.

With respect to the lateral strain energy releases depicted in FIGS.3M-N, leaflet 110 again experiences significant reductions as comparedto leaflet 72. In this example, the lateral strain energy release forleaflet 110 was determined to be 61.315 J/mm2 and the lateral strainenergy release for leaflet 72 was determined to be 71.097 J/mm2.

These significant reductions in strain energy release allows for the useof a wider range of materials in leaflets 110, such as those havinglower cut-growth thresholds that may exhibit superior overallperformance as compared to those having higher cut-growth thresholds.Alternatively, the same materials with high cut growth thresholds may beemployed but with prospects for longer lifetime in use.

Leaflets 110 are coupled to support structure 102 in a number of ways,such as adhesives, molding, casting, sewing, fasteners, and others knownto those of ordinary skill in the art. FIG. 5A is a flow diagramdepicting an example embodiment of a method 500 of manufacturing certainembodiments of prosthetic heart valve 100 using a dip casting process.At 502, a base frame is fabricated from a rigid material such as apolyether ether ketone (PEEK), a polyetherimide (PEI) such as ULTEM, andthe like. This can be done by machining or injection molding. At 504,the base frame is placed on a dipping mandrel that has the shape of theinterior surface of the support structure and leaflets. An exampleembodiment of a base frame 501 is depicted in the photograph of FIG. 5B.An example embodiment of a dipping mandrel 503, without the base frame,is depicted in the photograph of FIG. 5C. Mandrel 503 can be insertedinto a polymeric solution with forming equipment that envelops the baseframe and casts the leaflets in the desired form.

At 506, the base frame and mandrel is dipped in a polymeric solutionunder both high temperature and humidity and then withdrawn. Althoughthe methods disclosed herein are not limited to such, in some exampleembodiments, the relative humidity (RH) can be in the range of 20-80%and the temperature can be in the range of 20-50 degrees C. Step 506 canresult in a manifestation of support structure 102 and leaflets 111together in an integrally formed but unfinished state.

Dipping step 506 can be performed only once to arrive at the fullyformed (but unfinished) valve, or can be performed multiple times (e.g.,two times, three times, or as many times as desired). In one embodiment,the base frame is fabricated from a first material (e.g., PEEK)different than the polymeric material from which the leaflets arefabricated. In that case it may be desirable to form the leaflets to thebase frame only after the base frame has been pre-coated by the leafletpolymer to provide for greater cohesion. The base frame can bepre-coated by first dipping the base frame in the leaflet polymer havinga first viscosity. This can be done with or without the mandrel. If donewith the mandrel, the resulting leaflets can be removed. The pre-coatedbase frame can then be placed on the mandrel and dipped again, this timein the leaflet polymer with the same or a relatively higher viscosity.This second dipping can result in the formation of the full leafletbodies integrally formed with the support structure. Use of a lowviscosity followed by a higher viscosity can allow for formation of athin pre-coating that does not significantly distort the shape of theunderlying base frame followed by formation of the leaflets having thedesired thickness.

At 508, support structure 102 and leaflets 111 can be trimmed andotherwise finished to achieve accurate and precise edges and surfacesmoothness. This can occur, for example, through laser cutting,ultrasonic trimming, water knife, a mechanical clam shell cutter, andthe like. Finally, at 510, a sewing cuff can be coupled with supportstructure 102 and the final device can be packaged in the desiredsterile container.

Those of ordinary skill in the art will readily recognize, in light ofthis description, the many variations of suitable dip castingprocedures, pressures, and temperatures that are not stated here yet aresuitable to fabricate the prosthetic heart valves described herein.Likewise, those of ordinary skill in the art will also recognize, inlight of this description, the alternatives to dip casting that can beused to fabricate the prosthetic heart valves described herein.

As already mentioned, the embodiments of prosthetic heart valve 100described herein can be directly implanted into the heart of thepatient. In one such example procedure, the appropriate size replacementvalve can be determined and then an open heart access procedure isperformed by a surgeon to gain access to the malfunctioning valve of theheart that will be replaced. The surgeon can then position the selectedprosthetic heart valve 100 in position over the malfunctioning valve andattach valve 100 to the surrounding tissue. The attachment can occur,for instance, by fastening the sewing cuff to the tissue with one ormore sutures. Prior to attachment, if the surgeon determines that theselected valve size is not optimal, then a different valve having adifferent size can be selected and placed in position within the heart.In some other embodiments, the malfunctioning valve can be removed priorto positioning valve 100 in the intended location. Once valve 100 isattached, the open heart cavity is closed and the procedure is ended.

As used herein and in the appended claims, the singular forms “a”, “an”,and “the” include plural referents unless the context clearly dictatesotherwise.

It should be noted that all features, elements, components, functions,and steps described with respect to any embodiment provided herein areintended to be freely combinable and substitutable with those from anyother embodiment. If a certain feature, element, component, function, orstep is described with respect to only one embodiment, then it should beunderstood that that feature, element, component, function, or step canbe used with every other embodiment described herein unless explicitlystated otherwise. This paragraph therefore serves as antecedent basisand written support for the introduction of claims, at any time, thatcombine features, elements, components, functions, and steps fromdifferent embodiments, or that substitute features, elements,components, functions, and steps from one embodiment with those ofanother, even if the following description does not explicitly state, ina particular instance, that such combinations or substitutions arepossible. It is explicitly acknowledged that express recitation of everypossible combination and substitution is overly burdensome, especiallygiven that the permissibility of each and every such combination andsubstitution will be readily recognized by those of ordinary skill inthe art.

While the embodiments are susceptible to various modifications andalternative forms, specific examples thereof have been shown in thedrawings and are herein described in detail. It should be understood,however, that these embodiments are not to be limited to the particularform disclosed, but to the contrary, these embodiments are to cover allmodifications, equivalents, and alternatives falling within the spiritof the disclosure. Furthermore, any features, functions, steps, orelements of the embodiments may be recited in or added to the claims, aswell as negative limitations that define the inventive scope of theclaims by features, functions, steps, or elements that are not withinthat scope.

Other systems, devices, methods, features and advantages of the subjectmatter described herein will be or will become apparent to one withskill in the art upon examination of the following figures and detaileddescription. It is intended that all such additional systems, devices,methods, features and advantages be included within this description, bewithin the scope of the subject matter described herein, and beprotected by the accompanying claims. In no way should the features ofthe example embodiments be construed as limiting the appended claims,absent express recitation of those features in the claims.

What is claimed is:
 1. A prosthetic heart valve, comprising: a supportstructure having a central axis oriented in the direction of blood flowthrough an interior of the support structure; only three artificialleaflets, each leaflet having a movable part with a base along thesupport structure and a free edge allowed to move independent of thesupport structure, the movable part of each leaflet also having acentral axis extending between the base and the free edge, wherein themovable part of each leaflet is movable between a first position, forpreventing the flow of blood through an interior of the supportstructure, and a second position, for allowing the flow of blood throughthe interior of the support structure, wherein the base of the movablepart of each leaflet is the boundary where the movable part of theleaflet contacts the support structure, wherein the support structure issubstantially cylindrical where the base of the movable part of eachleaflet meets the support structure, and wherein a profile of the baseof the movable part of the first leaflet is at least partially convexwhen viewed from an exterior side view of the support structure normalto a plane formed by the central axis of the support structure and thecentral axis of the movable part of the first leaflet when in the firstposition.
 2. The prosthetic heart valve of claim 1, wherein the profileof the base of the movable part of the first leaflet is at leastpartially convex and at least partially concave when viewed from anexterior of the support structure along a normal to a plane formed bythe central axis of the support structure and the central axis of themovable part of the first leaflet.
 3. The prosthetic heart valve ofclaim 1, wherein, when a second one of the three leaflets is viewed froman exterior of the support structure along a normal to a plane formed bythe central axis of the support structure and the central axis of themovable part of the second leaflet, a profile of the base of the movablepart of the second leaflet is at least partially convex.
 4. Theprosthetic heart valve of claim 3, wherein, when a third one of thethree leaflets is viewed from an exterior of the support structure alonga normal to a plane formed by the central axis of the support structureand the central axis of the movable part of the third leaflet, a profileof the base of the movable part of the third leaflet is at leastpartially convex.
 5. The prosthetic heart valve of claim 1, wherein thesupport structure comprises an annular base portion at an upstream end.6. The prosthetic heart valve of claim 5, wherein the support structurecomprises a sewing cuff at the annular base portion.
 7. The prostheticheart valve of claim 5, wherein the support structure comprises aplurality of extensions from the annular base portion, with the base ofthe movable part of each leaflet meeting two adjacent ones of theextensions.
 8. The prosthetic heart valve of claim 1, wherein theartificial leaflets are polymeric.
 9. The prosthetic heart valve ofclaim 1, wherein the prosthetic heart valve is not radially collapsiblefor placement into an intravascular delivery device.
 10. The prostheticheart valve of claim 1, wherein the prosthetic heart valve is notradially collapsible for placement in a trans-apical delivery device.11. The prosthetic heart valve of claim 1, wherein the support structureand the plurality of leaflets are formed of the same material.
 12. Theprosthetic heart valve of claim 1, wherein the support structure and theplurality of leaflets are formed of different materials.
 13. Theprosthetic heart valve of claim 1, wherein each of the plurality ofleaflets is a discrete body.
 14. The prosthetic heart valve of claim 1,wherein the base of the movable part of each of the plurality ofleaflets is sewn to the support structure.
 15. The prosthetic heartvalve of claim 1, wherein the base of the movable part of each of thethree of leaflets is integrally formed to the support structure.
 16. Theprosthetic heart valve of claim 1, wherein the base of the movable partof each of the three of leaflets is a casting boundary between eachleaflet and the support structure.
 17. The prosthetic heart valve ofclaim 1, wherein the entirety of an inner lumen surface of the supportstructure is substantially cylindrical.
 18. The prosthetic heart valveof claim 1, wherein the support structure is cylindrical where the baseof the movable part of each leaflet transitions to the supportstructure.